Medical apparatus with scratch-resistant coating and method of making same

ABSTRACT

A method for providing a medical apparatus with a protective surface coating is described. The method comprises applying to a medical apparatus a coating solution that contains a matrix polymer such as a urethane, and a reinforcing agent such as lamellar platelet and fiber additives, as micaceous pigments, flake pigments, tungsten powder and glass fiber, to increase the resistance of the medical apparatus to injury, such that the surface coating forms a protective, scratch- and puncture-resistant layer on the medical apparatus. The particles or fibers of the reinforcing agent may be oriented to provide the medical apparatus with additional resistance to injury. The coating is well suited to provide balloon catheters, particularly PET balloons, and the like with the toughness desirable for use in stent delivery and placement.

This is a divisional of application Ser. No. 08/384,422 filed on Feb. 6,1995, now U.S. Pat. No. 5,599,576.

BACKGROUND OF THE INVENTION

As medical science delves into smaller areas of the body, such as bloodvessels, it has become increasingly difficult to reach these areas withan effective conventional apparatus. In part, this is due to thematerials from which the apparatus is made, and the dangers to theapparatus due to the methods of introduction into the body and inparticular, the small areas of the body. Particularly, catheters havinginflatable balloon attachments have been used for reaching these smalland related areas, such as in coronary angioplasty. More particularly,stent delivery and placement devices useful for opening occluded orblocked vessels have been used in coronary and peripheral angioplasty,urology and reproductive surgeries, among others.

Balloon catheters are produced from materials that can sustain largeamounts of pressure. However, the profile of balloon catheters andrelated devices must be small in order to be introduced into the smallareas of the bodies, such as blood vessels. Therefore, materials withhigh strength relative to film thickness are chosen. An example of thesematerials is PET (poly-ethylene terephthalate), which is useful forproviding a non-compliant, high-pressure device for delivering a stentto a vessel. Unfortunately, PET and other materials with high strengthto film thickness ratios tend to be scratch and puncture sensitive.Polymers that tend to be less sensitive to scratches, such aspolyethylene, nylon, and urethane are compliant, and at the same filmthickness as the non-compliant PET, do not provide the strength requiredto withstand the pressure used for delivering a stent into a vesselwall. Non-compliance, or the ability not to expand beyond apredetermined size on pressure and to maintain substantially a profile,is a desired characteristic for balloon catheters, particularly for usein small vessels, so as not to rupture or dissect the vessel as theballoon expands. A layer added on the substrate may provide someprotective characteristics to a medical apparatus by virtue of the addedthickness, and many resins may be used for this purpose. However, such aphysical barrier, provides only limited protection.

Further difficulties often arise in guiding a catheter into a desiredlocation in a patient due to the friction between the apparatus and thevessel through which the apparatus passes. The result of this frictionis failure of the balloon due to abrasion and puncture during handlingand use and also from over-inflation. There has been attention in thefield to providing lubricious coatings to the medical apparatus todiminish friction that causes apparatus failure. One such lubriciouscoating for balloon catheters is described in U.S. Pat. No. 5,272,012 toOpolski, wherein the use of a slip additive such as a siloxane isdisclosed. These coatings improve the success rates of balloon cathetersby altering the friction coefficient by use of lubricious coatings.However, they do not address the scratch and puncture-resistance of theapparatus other than by building film thickness, which is inadequateprotection against destruction of the balloon by tears, scratches,punctures and the like, particularly for the delivery of stentingdevices.

SUMMARY OF THE INVENTION

The present invention relates to a medical apparatus having and a methodfor providing a medical apparatus with a protective surface coatingcontaining a matrix polymer and a reinforcing agent to decrease thesensitivity of the medical apparatus to injuries, such as scratches,punctures, and the like. The reinforcing agent may be oriented in thecoating to provide enhanced injury resistance. The surface coating formsa protective layer on the medical apparatus to provide resistance toscratches, punctures and the like, and is well suited to an apparatusthat is required to withstand pressure and maintain a small profile.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention is described with reference to the Figures, which arepresented for the purpose of illustration only and which are in no wayintended to be limiting of the invention, and in which:

FIG. 1 is a cross-sectional view of a balloon medical device with theprotective coating of the invention; and

FIG. 2 is an expanded cross-sectional view of the section a-a' from FIG.1.

DETAILED DESCRIPTION OF THE INVENTION

In one aspect of the invention, a medical device having a protectivesurface coating is provided. FIG. 1 is a cross-sectional view of amedical device 10 comprising a balloon 11 coated with a protectivecoating 12 of the invention. FIG. 2 is an enlarged cross-sectional viewof the balloon as described in FIG. 1, along a-a', in which thecomponent elements of the device are clearly indicated. The protectivecoating 12 includes a matrix polymer 16 into which reinforcing agent 18is embedded. The reinforcing agent is preferably aligned parallel to thesurface of the medical device. An optional primer layer 14 may beinterposed between the balloon 10 and the protective layer 12.

As used herein, the term "medical apparatus" means apparatus suited foruse in medical applications, particularly in in vivo applications. Suchapparatus specifically includes, but is not limited to, balloons,catheters, guidewires, stylets and introducers. Of particular note foruse with the invention are catheters having inflatable balloons such asthose developed for use in angioplasty and valvuloplasty, urology,gynecology, neurology and the like.

As used herein, the term "reinforcing agent" means a substance capable,when in a coating, of increasing the hardness of the surface of amedical apparatus and allowing a fracture plane within the coatingwithout loss of coating from the substrate. Preferably, the reinforcingagent has a higher surface hardness than the surface hardness of themedical apparatus. Preferred reinforcing agents include lamellarplatelet and fiber additives, such as micaceous pigments, flakepigments, and glass. Glass fibers may be obtained pretreated withsilane, such as 737BC, available from Owens-Corning, Toledo, Ohio.

As used herein, the term "matrix polymer" means a polymer capable offorming a coating on the surface of a medical apparatus and providing anetwork for containing a reinforcing agent such as a solvent, water, UVcuring or 100% solids polymer. The matrix polymer preferably hasfunctional moieties capable of crosslinking to other moieties within thematrix polymer and with moieties derived from the medical apparatus toenhance the strength, adhesion and toughness of the coating. Examples ofmatrix polymers include resin systems such as urethane, acrylics, andepoxies or others selected for non-substrate attack and curingtemperature properties. Water-based urethanes are particularly desirabledue to their protective qualities allowing crosslinking within theurethane itself and binding with carboxyl groups present on the surfaceof the medical apparatus or derived at the surface with pretreatments orprimers.

The language "moieties derived from the medical apparatus" is intendedto include functional moieties from the material of which the medicalapparatus is made, moieties from a primer layer disposed between thecoating and the medical apparatus or moieties generated or formed bysubjecting the primer layer to a pretreatment step, e.g., plasma orcorona discharge.

In the case of most water-based coatings, e.g. urethane based, bondingof the coating to the substrate surface upon which it is applied can beachieved by use of an optional crosslinking agent, such that there isreaction between carboxyl functional groups present in the coating,e.g., urethane, and carboxyl functional groups present on the substratesurface. One method by which such bonding can be achieved involves acrosslinking reaction using polyfunctional aziridine through which thelinkage will occur. Crosslinking agents are added optionally to provideimproved hardness, adhesion and chemical and water resistance.

As used herein, the term "crosslinking agent" is intended to includeagents capable of enhancing the molecular weight of the matrix polymer.The crosslinking agent further may enhance the adhesion of the coatingto the medical apparatus. For example, functional moieties of the matrixpolymer may be crosslinked to the function moieties derived from themedical apparatus. The functional moieties are intended to includegroups capable of binding to one another. The matrix polymer may beselected for such functional moieties. Examples of crosslinking agentsuseful within this invention are aziridine, carbodiimides, ureaformaldehyde and melamine formaldehyde condensates, epoxies,isocyanates, titanates, zircoaluminates, zinc crosslinkers, and silanes.One skilled in the art would be able to select the crosslinking agentbased upon the functional moieties desired to be crosslinked and thesubstrate temperature limitations.

As used herein, the term "primer layer" is intended to include a layercapable of providing the desired adhesion to substrate and/or functionalmoieties for crosslinking to the matrix polymer or reinforcing agent.The primer layer is disposed between the medical apparatus and thematrix polymer. A material that is useful and desirable for makingmedical apparatus may not possess adhesion or functional moietiescapable of crosslinking sufficiently with a desired matrix polymer orreinforcing agent. In this situation, the desired adhesion or functionalmoieties can be provided to the surface of the medial apparatus bycoating the apparatus with a primer layer. An example of such a layer isa dispersion of ethylene acrylic acid (EAA), such as Primacor 5980available from Dow-Corning Corporation (Midland, Mich.), or MICHEMPRIME4983R available from Michelman (Cincinatti, Ohio), or which is capableof providing carboxyl moieties to the surface.

As an alternative to the use of a primer, a surface functionality can beobtained on the substrate surface using a number of other techniques.For example, surface functionality can be obtained using a plasma orcorona discharge or by exposing the surface to a flame. In the case ofplasma or corona discharge, the functionality obtained on the surfacecan be tailored through the use of process atmosphere variation. Thuswhen an oxygen-derived functionality (i.e. --OH or --COOH) is desired,the surface can be plasma treated in an oxygen-containing atmosphere.Alternatively, if an amine functionality is preferred, the treatingprocess can be carried out in a nitrogen containing atmosphere.

As used herein the term "coating solution" is intended to include asolution containing both the matrix polymer and the reinforcing agentcapable of being coated on a surface of a medical apparatus. The coatingsolution also may include other materials that do not detrimentallyeffect the protective compound and reinforcing agent network. Thesematerials include radiopacifiers, anti-slip additives, anti-maradditives, therapeutic agents, and antimicrobial agents. The termtherapeutic agent for purposes of this invention is intended to includesubstances capable of providing a therapeutic effect in the environmentof use of the medical apparatus. The therapeutic agents may beanti-inflammatory agents, antibiotics, immune-suppressible stimulatoryagents, anti-thrombolytic agents, growth factors, agents that locallyeffect blood pressure, agents that promote cell survival and healing,and the like. Antimicrobial agents are agents capable of suppressing thegrowth or activity of microorganism allowing them to combat infections.Examples of classes of antimicrobial agents include antibiotics, iodinesolutions, mercurials nitroimidazoles, bisguanidessilier, phenolics,ammonium salts, silver compounds and the like. Specific examples ofagents within classes include metronidazole and chlorhexidine. One ofordinary skill in the art would be able to select agents capable ofattaining a desired function or result.

The surface of the apparatus may be prepared for application of thecoating solution by pretreatment as needed for adhesion. Suchpreparation includes corona, plasma, flame and primer pretreatments.

The coating can be applied to a substrate using any of a variety ofmethods. Preferred among these are dipping, spraying, flowing, rollingand brushing. Orienting the particles or fibers of the reinforcing agentin the coating solution as it is applied to the medical apparatus isdesired. Orientation of the particles or fibers of the reinforcing agentso as to be aligned in a direction perpendicular to the direction oflikely injury, and may be accomplished by application shear, includingdip pull-out, direction rotation through solution, flow and spinorientation, surface tension and evaporative effects. A low solidscoating may be dipped more than once and may be most uniform forthickness, especially if oriented to allow sag to one end on one dip,and to a different orientation on a second dip. Possibilities exist fororienting by rotating through the coating on the axis of the apparatusand then drying in this configuration. Agitation may be needed duringapplication to maintain adequate consistency and inhibit skinning at thesurfaces. Such agitation will be required in accordance withmanufacturer's instructions in connection with the raw materials used,and may be based on the stability to shear of the reinforcing agent.

Film thickness of the coating is preferably in the range of about 0.1 toabout 3 mils, and most preferred in the range of about 0.5 to about 2mils. Adjustments to the viscosity and solids of the coating solutionwill accomplish the desired thickness and will be apparent to one ofordinary skill in the art. In the embodiment containing micaceouspigment as the reinforcing agent, the micaceous pigment concentrationshould be increased with decreasing thickness of film to allow increasedscratch and puncture resistance. The concentration of the reinforcingagent may be in the range of from about 1% to about 95% by weight ofsolids. The preferred concentration of reinforcing agent is in the rangeof about 10% to about 50% by weight of solids. However, too great aconcentration may degrade polymer properties and begin to affectperformance.

The curing may be carried out by first holding the coated apparatus atambient temperature to allow equilibration and foam to break. Air dryingis possible for ambient cure systems, and can be accelerated by heatcure at elevated temperature. Certain crosslinking agents may need acertain time at an elevated temperature to allow cure and this may beaccomplished by placing the coated apparatus in an oven, e.g. atapproximately 50° C. for a PET substrate, until the matrix polymer isfully dried. The temperature selected for the curing step may depend onthe temperature limitations of the substrate and the reactivity of thecrosslinking agent.

The resulting coating provides resistance to scratches, punctures andthe like, thereby decreasing the sensitivity of the medical apparatus toinjury. This decreased sensitivity is the result of the matrix polymerand the reinforcing agent in the coating solution. The coating solutioncontaining a matrix polymer and a reinforcing agent provides the coatingof the present invention with resistance to scratches, punctures and thelike that is enhanced over that which is provided by the matrix polymeralone. A reinforcing agent with a surface hardness that is higher thanthat of the surface hardness of the apparatus is preferred. Orientationof the fibers of the reinforcing agent so as to be aligned in adirection perpendicular to the direction of insertion into the body andsmall areas of the body is preferred. Micaceous or flake pigments usedas the reinforcing agent may be oriented parallel to the surface of thedevice.

EXAMPLE 1

A coating solution prepared in accordance with the teachings of thisinvention and having the following formulation is provided:

    ______________________________________                                        Component  Supplier/Designation                                                                        Weight (%)                                           ______________________________________                                        Urethane   R9621/Zeneca Resins                                                                         82.2                                                 Micaceous  110 Silver Pearl/                                                                           6.5                                                  pigment    EM Industries                                                      Crosslinking                                                                             CX100/Zeneca Resins                                                                         3.7                                                  Agent                                                                         Acetone    --            3.7                                                  Water      --            3.7                                                  ______________________________________                                    

The coating solution is prepared by prewetting and dispersing themicaceous pigment (3.5 g) (110 Silver Pearl obtained from EM Industries,Hawthorne, N.Y.) into a solution of distilled water (2 g) and acetone (2g) to reduce the tendency to foam. The urethane dispersion (44 g) (R9621obtained from Zeneca Resins, Wilmington, Mass.) was added with agitationprovided by a magnetic stirrer. Finally, the crosslinking agent (2 g)(CX100 obtained from Zeneca Resins) was added dropwise and allowed tostir for 30 minutes prior to application.

A PET balloon had been plasma treated (300 W, 0.25 Torr oxygen for 5minutes) and dipped into a 15% solids emulsion of primer (MICHEMPRIME4983R obtained from Michelman, Cincinatti, Ohio), and the then dried for5 minutes at 46° C. before the coating solution was applied. The coatingsolution was applied by dip, then cured and dried for 1 hour at 46° C.

EXAMPLE 2

A coating solution prepared in accordance with the teachings of thisinvention and having the following formulation is provided:

    ______________________________________                                        Component  Supplier/Designation                                                                         Weight (%)                                          ______________________________________                                        Urethane   R972 (Zeneca Resins)                                                                         50                                                  Glass fiber                                                                              737BC (Owens-Corning)                                                                        5.1                                                 Crosslinking                                                                             CX100/Zeneca Resins                                                                          2                                                   agent                                                                         Water      --             42.9                                                ______________________________________                                    

The urethane dispersion, glass fiber (737BC obtained from Owens-Corning,Toledo, Ohio) and water were mixed with agitation provided by a magneticstirrer. The crosslinking agent was added dropwise and allowed to stirfor 30 minutes prior to application.

The coating solution was applied to a PET balloon that had been coronatreated achieved by rotating the balloon for 1 minute within 1/2" ofcorona generated by a Model BD-20 with a 3" electrode, BD-20 supplied byElectro-Technics, Chicago, Ill.) and dipped into a 15% solids emulsionof primer (Primacor 5980, Dow Chemical, Midland, Mich.), and dried for 5minutes at 46° C. The coating solution was applied by flow coating, thencured and dried for 1 hour at 46° C.

EXAMPLE 3

A coating solution prepared in accordance with the teachings of thisinvention and having the following formulation is provided:

    ______________________________________                                        Component  Supplier/Designation                                                                            Weight (%)                                       ______________________________________                                        Urethane   R9621/Zeneca Resins                                                                              6.8                                             Water                        67.9                                             Tungsten Powder                                                                          M10/GTE Osram     23.2                                             Thickening ASE-60 Acrysol/Rohm & Haas                                                                       2.0                                             Agent                                                                         ______________________________________                                    

The coating solution was prepared by combining the urethane and water.The thickener may be added dropwise with agitation and the solution pHadjusted to 9 with ammonium hydroxide to allow the viscosity toincrease. The tungsten powder was added and stirred into the thickenedsolution.

A PET balloon prepared with a corona treatment (as in Example 2) andprimer dipped (MICHEMPRIME 4983 as in Example 1) was flow coated withthe tungsten reinforced coating solution and dried for 1 hour at 46° C.

Coated and uncoated balloons were scratch tested with the results thatthe testing of uncoated balloons resulted in complete destruction of theballoon, whereas the coated balloons resisted the injury, resulting inonly discrete damage to the effected area.

I claim:
 1. An insertable medical apparatus, having a protective surfacecoating, the coating comprising a matrix polymer containing areinforcing agent, said reinforcing agent being lamellar, platelet, orfiber-like in structure and having a higher surface hardness than thesurface hardness of the medical apparatus.
 2. A medical apparatus, inaccordance with claim 1, wherein the protective surface layer has athickness in the range of about 0.1 mil to about 3 mil.
 3. A medicalapparatus, in accordance with claim 2, wherein the protective surfacelayer further has a thickness in the range of about 0.5 mil to about 2mil.
 4. An insertable medical apparatus in accordance with claim 1 or 2,wherein the coating further comprises a crosslinking agent.
 5. A medicalapparatus in accordance with claim 4, wherein the crosslinking agent isselected from the group consisting of aziridine, carbodiimides, ureaformaldehyde, melamine formaldehyde condensates, epoxies, isocyanates,titanates, zircoaluminates, zinc crosslinkers, and silanes.
 6. Aninsertable medical apparatus in accordance with claim 1 or 2, themedical apparatus comprising a balloon for use with a catheter.
 7. Amedical apparatus in accordance with claim 1 or 2, the medical apparatusselected from the group consisting of balloon catheters, guide wires,and introducers.
 8. A medical apparatus in accordance with claim 1 or 2,wherein the protective surface layer comprises the outermost layer.
 9. Amedical apparatus in accordance with claim 1 or 2, wherein the matrixpolymer is selected from the group consisting of urethane, acrylic, andepoxy.
 10. A medical apparatus in accordance with claim 1 or 2, whereinthe reinforcing agent of the protective surface coating comprises amicaceous pigment.
 11. A medical apparatus in accordance with claim 1 or2, wherein the reinforcing agent of the protect surface coatingcomprises glass fiber.
 12. A medical apparatus in accordance with claim1 or 2, wherein the reinforcing agent is selected from the groupconsisting of lamellar platelet, flake pigments, tungsten powder, andfibers.
 13. A medical apparatus in accordance with claim 1 or 2, whereinthe coating further comprises an additive selected from the groupconsisting of radio pacifiers, anti-slip additives, anti-mar additives,and antimicrobial agents, and therapeutic agents.
 14. A medicalapparatus in accordance with claim 1 or 2, wherein the reinforcing agentis aligned in a direction parallel to the apparatus surface.
 15. Amedical apparatus in accordance with claim 1 or 2, wherein thereinforcing agent is present in an amount in the range of about 10% toabout 50% by weight of solids.
 16. A medical apparatus in accordancewith claim 15, wherein the therapeutic agent is selected from the groupconsisting of anti-inflammatory agents, antibiotics, immune-suppressiblestimulatory agents, anti-thrombolytic agents, growth factors, agentsthat locally affect blood pressure, and agents that promote or inhibitcell survival growth.
 17. A medical apparatus in accordance with claim15, wherein the antimicrobial agent is selected from the groupconsisting of antibiotics, iodine solutions, mercurial nitroimidazoles,bisguanidessilier, phenolics, ammonium salts, and silver compounds. 18.A medical apparatus in accordance with claim 1, further comprising aprimer layer disposed between the medical apparatus and the protectivesurface coating.
 19. A medical apparatus adapted for use within apatient having a protective surface coating, the coating comprising amatrix polymer containing a reinforcing agent, said reinforcing agenthaving a higher surface hardness than the surface hardness of themedical apparatus, wherein the protective surface coating has athickness in the range of about 0.1 mil to about 3 mil.